A0A3B6NKR6 is a GHMP kinase family protein from Triticum aestivum (bread wheat) that is predicted to function as a glucuronokinase (EC 2.7.1.43) based on its domain architecture. The protein contains GHMP kinase N-terminal (IPR006204) and C-terminal (IPR013750) domains together with a glucuronokinase-like domain (IPR053034). Glucuronokinases catalyze the ATP-dependent phosphorylation of D-glucuronic acid to D-glucuronate-1-phosphate, a key step in the myo-inositol oxidation pathway that provides an alternative route for UDP-glucuronic acid biosynthesis. UDP-glucuronic acid is a critical precursor for UDP-xylose, UDP-arabinose, and UDP-galacturonic acid, which are building blocks for hemicellulose and pectin biosynthesis. In wheat and other grasses with type II cell walls, arabinoxylan is the predominant hemicellulose, making enzymes in the UDP-glucuronic acid supply pathway particularly important for cell wall assembly. The protein is predicted to localize to the cytosol based on pathway context. This protein is unreviewed (TrEMBL) and has not been experimentally characterized; functional assignment rests on domain analysis, homology to characterized GHMP kinases (including Arabidopsis GLAK2, Q9LY82), and metabolic pathway inference.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
|
GO:0005829
cytosol
|
IBA
GO_REF:0000033 |
ACCEPT |
Summary: Cytosolic localization is consistent with the predicted glucuronokinase function. The myo-inositol oxidation pathway and UDP-sugar interconversion reactions that glucuronokinase participates in operate in the cytosol, where nucleotide sugar precursors are generated before transport to the Golgi for cell wall polysaccharide assembly. The IBA annotation is phylogenetically inferred from characterized orthologs (with/from includes MGI:MGI:107624 and PANTHER:PTN000048555).
|
|
GO:0005524
ATP binding
|
IEA
GO_REF:0000002 |
KEEP AS NON CORE |
Summary: ATP binding is well supported for a GHMP kinase family protein. GHMP kinases catalyze ATP-dependent phosphorylation of small-molecule substrates and contain conserved motifs for ATP binding. The InterPro-based IEA annotation from the GHMP kinase N-terminal domain (IPR006204) is appropriate but generic. This represents a necessary cofactor interaction for the predicted glucuronokinase activity rather than the primary molecular function.
Reason: ATP binding is a cofactor interaction intrinsic to kinase activity rather than the defining molecular function of this protein. The more informative annotation would be glucuronokinase activity (GO:0047940), which subsumes the ATP-binding aspect. Keeping as non-core since it is technically correct but not the primary functional descriptor.
|
|
GO:0019287
isopentenyl diphosphate biosynthetic process, mevalonate pathway
|
IEA
GO_REF:0000041 |
MARK AS OVER ANNOTATED |
Summary: This annotation is based on UniPathway mapping (UPA00057/UER00098) which associates the GHMP kinase domain family with the mevalonate pathway. However, the mevalonate pathway assignment is almost certainly incorrect for this protein. The GHMP kinase superfamily includes both mevalonate kinase and glucuronokinase, but this protein specifically contains a glucuronokinase-like domain (IPR053034), not a mevalonate kinase domain. Additionally, phmmer analysis identifies the closest characterized ortholog as Arabidopsis GLAK2 (Q9LY82, probable glucuronokinase 2, EC 2.7.1.43). The UniPathway mapping appears to be an over-broad family-level inference that incorrectly assigned a mevalonate pathway role based on GHMP kinase membership without considering the specific domain architecture.
Reason: The mevalonate pathway annotation is a family-level electronic annotation that does not account for the protein's specific glucuronokinase-like domain (IPR053034). The protein is most likely involved in UDP-glucuronic acid biosynthesis via the myo-inositol oxidation pathway, not the mevalonate pathway. This is a classic case of over-broad IEA annotation from superfamily membership.
|
|
GO:0047940
glucuronokinase activity
|
IEA | NEW |
Summary: Not currently in GOA but strongly supported by domain architecture. The protein contains a glucuronokinase-like domain (IPR053034) and its closest characterized ortholog is Arabidopsis GLAK2 (Q9LY82, EC 2.7.1.43). Glucuronokinase activity is the most specific and informative molecular function term for this protein.
Reason: Proposed based on glucuronokinase-like domain (IPR053034) and orthology to Arabidopsis GLAK2. More informative than the current generic ATP binding annotation.
|
|
GO:0006065
UDP-glucuronate biosynthetic process
|
IEA | NEW |
Summary: Not currently in GOA. Glucuronokinase generates D-glucuronate-1-phosphate, the immediate precursor for UDP-glucuronic acid biosynthesis via the myo-inositol oxidation pathway. This is a more accurate biological process annotation than the current mevalonate pathway assignment.
Reason: Proposed as a replacement for the incorrect mevalonate pathway annotation. UDP-glucuronate biosynthesis is the correct pathway context based on the glucuronokinase-like domain and orthology evidence.
|
The research report should be a detailed narrative explaining the function, biological processes, and localization of the gene product. Citations should be given for all claims.
You should prioritize authoritative reviews and primary scientific literature when conducting research. You can supplement
this with annotations you find in gene/protein databases, but these can be outdated or inaccurate.
We are specifically interested in the primary function of the gene - for enzymes, what reaction is catalyzed, and what is the substrate specificity? For transporters, what is the substrate? For structural proteins or adapters, what is the broader structural role? For signaling molecules, what is the role in the pathway.
We are interested in where in or outside the cell the gene product carries out its function.
We are also interested in the signaling or biochemical pathways in which the gene functions. We are less interested in broad pleiotropic effects, except where these elucidate the precise role.
Include evidence where possible. We are interested in both experimental evidence as well as inference from structure, evolution, or bioinformatic analysis. Precise studies should be prioritized over high-throughput, where available.
The protein A0A3B6NKR6 from Triticum aestivum (wheat) is a computationally annotated GHMP kinase N-terminal domain-containing protein that, based on domain architecture and pathway analysis, most likely functions as a glucuronokinase. No direct experimental characterization of this specific wheat protein was found in the available literature. However, functional inference from domain analysis, GHMP kinase family characteristics, and plant UDP-sugar metabolism studies provides strong evidence for its role in nucleotide sugar biosynthesis and cell wall metabolism.
A0A3B6NKR6 is annotated in UniProt as a GHMP kinase N-terminal domain-containing protein from Triticum aestivum. The protein contains three key domains: GHMP_kinase_N_dom (IPR006204), GHMP_kinase_C_dom (IPR013750), and a Glucuronokinase-like domain (IPR053034) (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2). These domains place the protein within the GHMP kinase superfamily, a structurally conserved family of small-molecule kinases named for its founding members: galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, aoki2022crystalstructureof pages 1-2).
The GHMP kinase superfamily is characterized by a conserved structural fold consisting of N-terminal and C-terminal domains that together form the active site for ATP-dependent phosphorylation reactions (aoki2022crystalstructureof pages 2-4). Members of this family share common catalytic mechanisms despite catalyzing reactions on different substrates, and they are generally intolerant to single amino acid substitutions, indicating strong selective pressure to maintain their structural and functional integrity (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2).
The presence of the glucuronokinase-like domain strongly suggests that A0A3B6NKR6 functions as a glucuronokinase (also known as GluK or glucuronate kinase). Glucuronokinase catalyzes the ATP-dependent phosphorylation of D-glucuronic acid to produce glucuronate-1-phosphate, a key intermediate in the myo-inositol oxidation pathway (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4).
The predicted enzymatic reaction is:
D-glucuronic acid + ATP → D-glucuronate-1-phosphate + ADP
Based on the glucuronokinase annotation and by analogy to characterized GHMP kinases, the enzyme likely exhibits the following substrate preferences:
- Primary substrate: D-glucuronic acid
- Phosphate donor: ATP
- Cofactor requirements: Mg²⁺ or other divalent cations (typical for GHMP kinases)
GHMP kinases generally follow an ordered ternary complex mechanism in which ATP binds first to the enzyme, followed by the sugar substrate (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2). Although the specific kinetic parameters for this wheat protein have not been determined experimentally, this catalytic strategy is highly conserved across the GHMP family.
As a GHMP kinase family member, A0A3B6NKR6 is expected to utilize conserved catalytic residues for substrate binding and phosphoryl transfer. GHMP kinases typically employ key aspartate or glutamate residues as catalytic bases, along with conserved histidine residues that stabilize transition states during phosphoryl transfer (aoki2022crystalstructureof pages 1-2, aoki2022crystalstructureof pages 2-4). The enzyme adopts the characteristic GHMP fold, which creates a deep cleft for substrate binding surrounded by α-helices and β-sheets (aoki2022crystalstructureof pages 2-4).
Based on the metabolic pathway context, A0A3B6NKR6 most likely localizes to the cytosol. The myo-inositol oxidation pathway, which includes glucuronokinase, operates in the cytosolic compartment where it generates UDP-glucuronic acid and related nucleotide sugars that serve as precursors for cell wall polysaccharide biosynthesis (mason2023organspecificexpressionof pages 1-3, pagliuso2021genomemappingand pages 1-4). These nucleotide sugars are subsequently transported into the Golgi apparatus where they are utilized by glycosyltransferases for hemicellulose and pectin synthesis.
Glucuronokinase functions as a critical enzyme in the myo-inositol oxidation pathway, which provides an alternative route for UDP-glucuronic acid biosynthesis (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4). This pathway operates as follows:
This pathway represents an important metabolic flexibility mechanism, providing an alternative to the more direct route through UDP-glucose dehydrogenase (UGD), which converts UDP-glucose directly to UDP-glucuronic acid (mason2023organspecificexpressionof pages 1-3).
UDP-glucuronic acid, the downstream product of the glucuronokinase pathway, serves as a critical branch point in plant nucleotide sugar metabolism (zhang2021biosynthesisandtransport pages 1-3, mason2023organspecificexpressionof pages 1-3). It is the precursor for several essential UDP-sugars:
In wheat and other grasses, which possess type II cell walls, arabinoxylans represent the predominant hemicellulose component (zhang2021biosynthesisandtransport pages 1-3, pagliuso2021genomemappingand pages 1-4). Therefore, enzymes involved in UDP-glucuronic acid metabolism, including glucuronokinase, are particularly important for providing the nucleotide sugar precursors required for arabinoxylan biosynthesis and cell wall assembly.
Studies in sugarcane (Saccharum spp.) have demonstrated that genes involved in UDP-glucose metabolism, including the myo-inositol pathway genes (glucuronokinase, myo-inositol oxygenase), play significant roles in carbon partitioning between different metabolic pools (mason2023organspecificexpressionof pages 1-3). Gene expression analysis revealed that these pathway components show organ-specific expression patterns, with higher expression in tissues undergoing active cell wall biosynthesis and growth (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4).
The myo-inositol pathway provides metabolic flexibility by serving as an alternative route to UDP-glucuronic acid when the direct UDP-glucose dehydrogenase pathway is limiting or downregulated. This flexibility is important for maintaining cell wall biosynthesis under varying physiological conditions (mason2023organspecificexpressionof pages 3-4).
The myo-inositol pathway also contributes to ascorbic acid (vitamin C) biosynthesis in plants (yan2022integrativetranscriptomeand pages 1-2). D-glucuronic acid and UDP-glucuronic acid can be channeled into the ascorbate biosynthetic pathway, where they are converted through a series of enzymatic steps to L-ascorbic acid. This connection between cell wall precursor metabolism and antioxidant biosynthesis highlights the multifunctional nature of the glucuronokinase pathway.
Studies in quinoa and other plants have shown that genes associated with UDP-sugar metabolism and the myo-inositol pathway are regulated under abiotic stress conditions (salt, drought, ABA treatment), potentially reflecting changes in both cell wall remodeling and ascorbic acid-mediated stress responses (yan2022integrativetranscriptomeand pages 1-2).
In wheat (Triticum aestivum), a cereal crop with type II cell walls enriched in arabinoxylan and β-glucan hemicelluloses, the enzymes supporting UDP-glucuronic acid biosynthesis are likely critical for:
Cell wall assembly and biomass properties: Arabinoxylans constitute the major non-cellulosic polysaccharide in wheat cell walls, particularly in the grain endosperm and vegetative tissues. UDP-glucuronic acid derivatives provide the building blocks for these polymers (zhang2021biosynthesisandtransport pages 1-3, pagliuso2021genomemappingand pages 1-4).
Growth and development: Cell wall biosynthesis is tightly coupled with cell expansion and tissue differentiation. Glucuronokinase-mediated nucleotide sugar supply would be expected to support these developmental processes.
Biomass quality for end-use applications: The composition and structure of arabinoxylans influence wheat grain quality, dough properties, and nutritional characteristics. Enzymes in nucleotide sugar metabolism are therefore relevant to both agricultural productivity and food processing qualities.
Stress adaptation: The connection between the myo-inositol pathway and ascorbic acid biosynthesis suggests potential roles in oxidative stress management and environmental adaptation (yan2022integrativetranscriptomeand pages 1-2).
It is important to note that no direct experimental characterization of A0A3B6NKR6 was identified in the available scientific literature. The functional annotation presented here is based on:
While this approach provides a moderate to high confidence functional prediction as a putative glucuronokinase involved in UDP-glucuronic acid biosynthesis, definitive experimental validation would require:
- Heterologous expression and biochemical characterization to confirm enzymatic activity
- Substrate specificity assays to verify glucuronic acid as the preferred substrate
- Subcellular localization studies in wheat tissues
- Genetic knockout or knockdown studies to assess physiological roles
- Transcriptional profiling across wheat developmental stages and stress conditions
One potentially relevant study that could not be accessed is Thakur et al. (2021) published in Plant Molecular Biology Reporter, which reportedly conducted genome-wide identification and analysis of the GHMP kinase gene superfamily in bread wheat. This work may contain additional information about A0A3B6NKR6 or related family members.
| Protein Feature | Description/Details | Evidence Type | References/Citations |
|---|---|---|---|
| UniProt accession | A0A3B6NKR6; UniProt entry described as “GHMP kinase N-terminal domain-containing protein” from wheat. No experimentally validated gene symbol was identified in the available literature for this exact accession. | Database annotation; literature verification found no direct paper on this exact accession | (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2) |
| Protein name | Predicted GHMP kinase N-terminal domain-containing protein; based on domain content, the most plausible functional annotation is putative glucuronokinase rather than a generic GHMP kinase. | Computational annotation refined by domain-based functional inference | (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, mason2023organspecificexpressionof pages 1-3) |
| Organism | Triticum aestivum (bread wheat), a grass with type II cell walls enriched in arabinoxylan/other hemicellulosic polysaccharides, increasing the likely importance of UDP-sugar metabolism. | Database annotation plus plant cell-wall context from grass literature | (pagliuso2021genomemappingand pages 1-4, zhang2021biosynthesisandtransport pages 1-3) |
| Domain architecture | UniProt-supplied domains include GHMP_kinase_N_dom, GHMP_kinase_C_dom, and Glucuronokinase-like. GHMP kinases are a structurally conserved superfamily of small-molecule kinases with N- and C-terminal domains. | Domain analysis; superfamily inference from structural/functional literature | (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, aoki2022crystalstructureof pages 2-4) |
| GHMP kinase family context | GHMP denotes galactokinase, homoserine kinase, mevalonate kinase, and phosphomevalonate kinase. Members catalyze ATP-dependent phosphorylation of small metabolites and share conserved structural features and catalytic logic. | Homology-based family inference from authoritative review/primary literature | (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, aoki2022crystalstructureof pages 2-4, garay2026themevalonatepathway pages 3-5) |
| Predicted enzymatic function | Most likely glucuronokinase (EC class kinase activity) that phosphorylates D-glucuronic acid in the myo-inositol/UDP-sugar pathway. This inference is strongly supported by the specific glucuronokinase-like annotation in the domain architecture. | Domain analysis; pathway inference from plant UDP-sugar metabolism literature | (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4) |
| Substrate specificity | Predicted preferred substrate: D-glucuronic acid; phosphate donor: ATP. By analogy to GHMP kinases, ATP likely binds first in an ordered ternary complex mechanism, although this has not been shown directly for A0A3B6NKR6. | Inference from glucuronokinase-like annotation and GHMP kinase catalytic behavior | (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, mason2023organspecificexpressionof pages 1-3) |
| Reaction catalyzed | Most likely reaction: D-glucuronic acid + ATP → D-glucuronate-1-phosphate + ADP. This is the expected glucuronokinase step feeding UDP-glucuronic acid biosynthesis via the myo-inositol-derived route. | Biochemical inference from pathway placement and glucuronokinase annotation | (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4) |
| Catalytic/mechanistic features | As a GHMP-family enzyme, the protein is expected to adopt the characteristic GHMP fold and perform ATP-dependent small-molecule phosphorylation. GHMP kinases are structurally conserved and often sensitive to amino-acid substitutions affecting catalysis or substrate binding. | Structural/mechanistic homology inference | (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, aoki2022crystalstructureof pages 2-4) |
| Probable subcellular localization | Most likely cytosolic, because the myo-inositol oxidation/UDP-sugar interconversion pathway supplying cell-wall precursors is generally described as part of cytosolic carbohydrate metabolism prior to Golgi/plasma-membrane polymer assembly. No direct localization data were found for this wheat protein. | Pathway-based inference; no direct localization experiment for this accession | (mason2023organspecificexpressionof pages 1-3, pagliuso2021genomemappingand pages 1-4) |
| Key biochemical pathway | Likely part of the myo-inositol oxidation pathway: myo-inositol → D-glucuronic acid (via MIOX) → glucuronate-1-phosphate (via glucuronokinase/GluK) → UDP-glucuronic acid → downstream UDP-sugars. This pathway provides an alternative route to UDP-glucuronic acid besides UDP-glucose dehydrogenase. | Pathway reconstruction from plant UDP-glucose/UDP-sugar metabolism studies | (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4) |
| Downstream metabolic products | The predicted product pool includes UDP-glucuronic acid, which can be converted into UDP-xylose and other nucleotide sugars used for hemicellulose and cell-wall polysaccharide biosynthesis. | Pathway inference from plant nucleotide-sugar biosynthesis literature | (zhang2021biosynthesisandtransport pages 1-3, mason2023organspecificexpressionof pages 1-3, pagliuso2021genomemappingand pages 1-4) |
| Biological process | Likely contributes to cell-wall precursor biosynthesis, carbon partitioning, and potentially ascorbate-related metabolism/stress responses through the myo-inositol pathway. | Inference from plant pathway studies and transcriptomic context | (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4, yan2022integrativetranscriptomeand pages 1-2) |
| Relevance to wheat biology | In grasses such as wheat, cell walls are rich in arabinoxylan/xylan-related hemicelluloses. Therefore, enzymes supporting UDP-glucuronic acid and derivative sugar-nucleotide supply are likely important for wall formation, growth, biomass properties, and possibly stress adaptation. | Species-context inference from grass cell-wall composition and plant UDP-sugar metabolism | (zhang2021biosynthesisandtransport pages 1-3, pagliuso2021genomemappingand pages 1-4) |
| Expression/physiological context from plants | In sugarcane, genes in the UDP-glucose/myo-inositol pathway, including GluK, are discussed in the context of organ-specific carbon partitioning and tissues with active growth/cell-wall synthesis. In quinoa, glucuronokinase-associated pathways appear among salt-responsive metabolic changes. | Comparative plant transcriptomic evidence; indirect support | (mason2023organspecificexpressionof pages 1-3, yan2022integrativetranscriptomeand pages 1-2) |
| Confidence and limitations | Moderate confidence for assignment as a putative glucuronokinase based on domain architecture and pathway logic; low confidence for exact localization, regulation, and kinetic properties because no direct experimental study of A0A3B6NKR6 was identified in the available sources. | Evidence grading based on presence/absence of direct accession-specific data | (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, mason2023organspecificexpressionof pages 1-3) |
Table: This table summarizes the available evidence for functional annotation of wheat protein A0A3B6NKR6. Because direct literature on this accession is lacking, the annotation relies primarily on domain architecture, GHMP kinase family properties, and plant UDP-sugar pathway context.
A0A3B6NKR6 from Triticum aestivum is most plausibly annotated as a putative glucuronokinase based on its domain architecture containing GHMP kinase N-terminal and C-terminal domains plus a glucuronokinase-like domain (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2). The enzyme likely catalyzes the ATP-dependent phosphorylation of D-glucuronic acid to glucuronate-1-phosphate as part of the myo-inositol oxidation pathway (mason2023organspecificexpressionof pages 1-3). This pathway provides UDP-glucuronic acid for downstream nucleotide sugar biosynthesis, supporting cell wall polysaccharide assembly—particularly important in wheat given its arabinoxylan-rich type II cell walls (zhang2021biosynthesisandtransport pages 1-3, pagliuso2021genomemappingand pages 1-4).
The protein is expected to function in the cytosol, where it participates in carbon partitioning and metabolic flexibility between different nucleotide sugar biosynthetic routes (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4). Beyond its primary role in cell wall precursor metabolism, the pathway may also contribute to ascorbic acid biosynthesis and stress responses (yan2022integrativetranscriptomeand pages 1-2).
While the functional inference is strongly supported by domain analysis and comparative pathway biology, direct experimental validation of A0A3B6NKR6's enzymatic activity, substrate specificity, localization, and physiological roles in wheat remains to be conducted. Future studies characterizing this and related GHMP kinase family members in wheat will be valuable for understanding nucleotide sugar metabolism and its regulation in this agriculturally important cereal crop.
The functional annotation is primarily based on:
- GHMP kinase family structure and catalysis (rubiogozalbo2021galactokinasedeficiencylessons pages 1-2, aoki2022crystalstructureof pages 1-2, aoki2022crystalstructureof pages 2-4, garay2026themevalonatepathway pages 3-5)
- Plant UDP-sugar and nucleotide sugar metabolism (zhang2021biosynthesisandtransport pages 1-3, mason2023organspecificexpressionof pages 1-3, pagliuso2021genomemappingand pages 1-4)
- Myo-inositol pathway and glucuronokinase function (mason2023organspecificexpressionof pages 1-3, mason2023organspecificexpressionof pages 3-4)
- Plant stress responses and metabolic regulation (yan2022integrativetranscriptomeand pages 1-2)
- Cell wall biosynthesis in grasses (zhang2021biosynthesisandtransport pages 1-3, pagliuso2021genomemappingand pages 1-4)
References
(rubiogozalbo2021galactokinasedeficiencylessons pages 1-2): M. Estela Rubio-Gozalbo, Britt Derks, Anibh Martin Das, Uta Meyer, Dorothea Möslinger, M. Luz Couce, Aurélie Empain, Can Ficicioglu, Natalia Juliá Palacios, Mariela M. De Los Santos De Pelegrin, Isabel A. Rivera, Sabine Scholl-Bürgi, Annet M. Bosch, David Cassiman, Didem Demirbas, Matthias Gautschi, Ina Knerr, Philippe Labrune, Anastasia Skouma, Patrick Verloo, Saskia B. Wortmann, Eileen P. Treacy, David J. Timson, and Gerard T. Berry. Galactokinase deficiency: lessons from the galnet registry. Genetics in Medicine, 23:202-210, Jan 2021. URL: https://doi.org/10.1038/s41436-020-00942-9, doi:10.1038/s41436-020-00942-9. This article has 39 citations and is from a highest quality peer-reviewed journal.
(aoki2022crystalstructureof pages 1-2): Mizuki Aoki, Jeffrey Vinokur, Kento Motoyama, Rino Ishikawa, Michael Collazo, Duilio Cascio, Michael R. Sawaya, Tomokazu Ito, James U. Bowie, and Hisashi Hemmi. Crystal structure of mevalonate 3,5-bisphosphate decarboxylase reveals insight into the evolution of decarboxylases in the mevalonate metabolic pathways. Jul 2022. URL: https://doi.org/10.1016/j.jbc.2022.102111, doi:10.1016/j.jbc.2022.102111. This article has 8 citations and is from a domain leading peer-reviewed journal.
(aoki2022crystalstructureof pages 2-4): Mizuki Aoki, Jeffrey Vinokur, Kento Motoyama, Rino Ishikawa, Michael Collazo, Duilio Cascio, Michael R. Sawaya, Tomokazu Ito, James U. Bowie, and Hisashi Hemmi. Crystal structure of mevalonate 3,5-bisphosphate decarboxylase reveals insight into the evolution of decarboxylases in the mevalonate metabolic pathways. Jul 2022. URL: https://doi.org/10.1016/j.jbc.2022.102111, doi:10.1016/j.jbc.2022.102111. This article has 8 citations and is from a domain leading peer-reviewed journal.
(mason2023organspecificexpressionof pages 1-3): Patrick J. Mason, Nam V. Hoang, Frederik C. Botha, Agnelo Furtado, Annelie Marquardt, and Robert J. Henry. Organ-specific expression of genes associated with the udp-glucose metabolism in sugarcane (saccharum spp. hybrids). BMC Genomics, Jan 2023. URL: https://doi.org/10.1186/s12864-023-09124-8, doi:10.1186/s12864-023-09124-8. This article has 9 citations and is from a peer-reviewed journal.
(mason2023organspecificexpressionof pages 3-4): Patrick J. Mason, Nam V. Hoang, Frederik C. Botha, Agnelo Furtado, Annelie Marquardt, and Robert J. Henry. Organ-specific expression of genes associated with the udp-glucose metabolism in sugarcane (saccharum spp. hybrids). BMC Genomics, Jan 2023. URL: https://doi.org/10.1186/s12864-023-09124-8, doi:10.1186/s12864-023-09124-8. This article has 9 citations and is from a peer-reviewed journal.
(pagliuso2021genomemappingand pages 1-4): Debora Pagliuso, Bruno Viana Navarro, Adriana Grandis, Marcelo M. Zerillo, Eric Lam, and Marcos Silveira Buckeridge. Genome mapping and gene expression of ndp-sugar pathways in the giant duckweed spirodela polyrhiza and its relevance for bioenergy. ArXiv, Aug 2021. URL: https://doi.org/10.21203/rs.3.rs-776424/v1, doi:10.21203/rs.3.rs-776424/v1. This article has 0 citations.
(zhang2021biosynthesisandtransport pages 1-3): Wenjuan Zhang, Wenqi Qin, Huiling Li, and Ai-min Wu. Biosynthesis and transport of nucleotide sugars for plant hemicellulose. Frontiers in Plant Science, Nov 2021. URL: https://doi.org/10.3389/fpls.2021.723128, doi:10.3389/fpls.2021.723128. This article has 84 citations.
(yan2022integrativetranscriptomeand pages 1-2): Huifang Yan, Yuting Nie, Kailun Cui, and Juan Sun. Integrative transcriptome and metabolome profiles reveal common and unique pathways involved in seed initial imbibition under artificial and natural salt stresses during germination of halophyte quinoa. Frontiers in Plant Science, Apr 2022. URL: https://doi.org/10.3389/fpls.2022.853326, doi:10.3389/fpls.2022.853326. This article has 22 citations.
(garay2026themevalonatepathway pages 3-5): Aisel Valle Garay, Cíntia Marques Coelho, Napoleão Fonseca Valadares, Leonardo Ferreira da Silva, Letícia Sousa Cabral, Matheus Castro Leitão, Luiza Cesca Piva, Janice Lisboa De Marco, Brenda Rabello de Camargo, Amanda Araújo Souza, Izadora Cristina Moreira de Oliveira, Matheus Ferroni Schwartz, Túlio Marcos Godoy de Andrade, Talita Souza Carmo, João Ricardo Moreira de Almeida, Fernando Araripe Gonçalves Torres, and Sonia Maria de Freitas. The mevalonate pathway: characteristics, innovations, applications, and challenges in biotechnology. Unknown journal, May 2026. URL: https://doi.org/10.20944/preprints202605.0182.v1, doi:10.20944/preprints202605.0182.v1.
id: A0A3B6NKR6
gene_symbol: A0A3B6NKR6
product_type: PROTEIN
status: COMPLETE
taxon:
id: NCBITaxon:4565
label: Triticum aestivum
description: >-
A0A3B6NKR6 is a GHMP kinase family protein from Triticum aestivum (bread wheat) that is
predicted to function as a glucuronokinase (EC 2.7.1.43) based on its domain architecture.
The protein contains GHMP kinase N-terminal (IPR006204) and C-terminal (IPR013750) domains
together with a glucuronokinase-like domain (IPR053034). Glucuronokinases catalyze the
ATP-dependent phosphorylation of D-glucuronic acid to D-glucuronate-1-phosphate, a key
step in the myo-inositol oxidation pathway that provides an alternative route for
UDP-glucuronic acid biosynthesis. UDP-glucuronic acid is a critical precursor for
UDP-xylose, UDP-arabinose, and UDP-galacturonic acid, which are building blocks for
hemicellulose and pectin biosynthesis. In wheat and other grasses with type II cell walls,
arabinoxylan is the predominant hemicellulose, making enzymes in the UDP-glucuronic acid
supply pathway particularly important for cell wall assembly. The protein is predicted to
localize to the cytosol based on pathway context. This protein is unreviewed (TrEMBL) and
has not been experimentally characterized; functional assignment rests on domain analysis,
homology to characterized GHMP kinases (including Arabidopsis GLAK2, Q9LY82), and
metabolic pathway inference.
existing_annotations:
- term:
id: GO:0005829
label: cytosol
evidence_type: IBA
original_reference_id: GO_REF:0000033
qualifier: is_active_in
review:
summary: >-
Cytosolic localization is consistent with the predicted glucuronokinase function.
The myo-inositol oxidation pathway and UDP-sugar interconversion reactions that
glucuronokinase participates in operate in the cytosol, where nucleotide sugar
precursors are generated before transport to the Golgi for cell wall polysaccharide
assembly. The IBA annotation is phylogenetically inferred from characterized
orthologs (with/from includes MGI:MGI:107624 and PANTHER:PTN000048555).
action: ACCEPT
- term:
id: GO:0005524
label: ATP binding
evidence_type: IEA
original_reference_id: GO_REF:0000002
qualifier: enables
review:
summary: >-
ATP binding is well supported for a GHMP kinase family protein. GHMP kinases
catalyze ATP-dependent phosphorylation of small-molecule substrates and contain
conserved motifs for ATP binding. The InterPro-based IEA annotation from the GHMP
kinase N-terminal domain (IPR006204) is appropriate but generic. This represents
a necessary cofactor interaction for the predicted glucuronokinase activity rather
than the primary molecular function.
action: KEEP_AS_NON_CORE
reason: >-
ATP binding is a cofactor interaction intrinsic to kinase activity rather than the
defining molecular function of this protein. The more informative annotation would
be glucuronokinase activity (GO:0047940), which subsumes the ATP-binding aspect.
Keeping as non-core since it is technically correct but not the primary functional
descriptor.
- term:
id: GO:0019287
label: isopentenyl diphosphate biosynthetic process, mevalonate pathway
evidence_type: IEA
original_reference_id: GO_REF:0000041
qualifier: involved_in
review:
summary: >-
This annotation is based on UniPathway mapping (UPA00057/UER00098) which associates
the GHMP kinase domain family with the mevalonate pathway. However, the mevalonate
pathway assignment is almost certainly incorrect for this protein. The GHMP kinase
superfamily includes both mevalonate kinase and glucuronokinase, but this protein
specifically contains a glucuronokinase-like domain (IPR053034), not a mevalonate
kinase domain. Additionally, phmmer analysis identifies the closest characterized
ortholog as Arabidopsis GLAK2 (Q9LY82, probable glucuronokinase 2, EC 2.7.1.43).
The UniPathway mapping appears to be an over-broad family-level inference that
incorrectly assigned a mevalonate pathway role based on GHMP kinase membership
without considering the specific domain architecture.
action: MARK_AS_OVER_ANNOTATED
reason: >-
The mevalonate pathway annotation is a family-level electronic annotation that
does not account for the protein's specific glucuronokinase-like domain
(IPR053034). The protein is most likely involved in UDP-glucuronic acid
biosynthesis via the myo-inositol oxidation pathway, not the mevalonate pathway.
This is a classic case of over-broad IEA annotation from superfamily membership.
- term:
id: GO:0047940
label: glucuronokinase activity
evidence_type: IEA
qualifier: enables
review:
summary: >-
Not currently in GOA but strongly supported by domain architecture. The protein
contains a glucuronokinase-like domain (IPR053034) and its closest characterized
ortholog is Arabidopsis GLAK2 (Q9LY82, EC 2.7.1.43). Glucuronokinase activity
is the most specific and informative molecular function term for this protein.
action: NEW
reason: >-
Proposed based on glucuronokinase-like domain (IPR053034) and orthology to
Arabidopsis GLAK2. More informative than the current generic ATP binding annotation.
- term:
id: GO:0006065
label: UDP-glucuronate biosynthetic process
evidence_type: IEA
qualifier: involved_in
review:
summary: >-
Not currently in GOA. Glucuronokinase generates D-glucuronate-1-phosphate, the
immediate precursor for UDP-glucuronic acid biosynthesis via the myo-inositol
oxidation pathway. This is a more accurate biological process annotation than the
current mevalonate pathway assignment.
action: NEW
reason: >-
Proposed as a replacement for the incorrect mevalonate pathway annotation.
UDP-glucuronate biosynthesis is the correct pathway context based on the
glucuronokinase-like domain and orthology evidence.
core_functions:
- description: >-
Predicted glucuronokinase that catalyzes the ATP-dependent phosphorylation of
D-glucuronic acid to D-glucuronate-1-phosphate in the myo-inositol oxidation
pathway, providing an alternative route for UDP-glucuronic acid biosynthesis and
supplying nucleotide sugar precursors for cell wall polysaccharide assembly in wheat
supported_by:
- reference_id: file:WHEAT/A0A3B6NKR6/A0A3B6NKR6-deep-research-falcon.md
supporting_text: >-
The presence of the glucuronokinase-like domain strongly suggests that A0A3B6NKR6
functions as a glucuronokinase (also known as GluK or glucuronate kinase).
Glucuronokinase catalyzes the ATP-dependent phosphorylation of D-glucuronic acid
to produce glucuronate-1-phosphate, a key intermediate in the myo-inositol
oxidation pathway
molecular_function:
id: GO:0047940
label: glucuronokinase activity
directly_involved_in:
- id: GO:0006065
label: UDP-glucuronate biosynthetic process
locations:
- id: GO:0005829
label: cytosol
references:
- id: file:WHEAT/A0A3B6NKR6/A0A3B6NKR6-deep-research-falcon.md
title: Deep research report for A0A3B6NKR6 (GHMP kinase N-terminal domain-containing protein) in Triticum aestivum
findings:
- statement: >-
A0A3B6NKR6 contains GHMP kinase N-terminal, C-terminal, and glucuronokinase-like
domains, and is most plausibly annotated as a putative glucuronokinase involved in
UDP-glucuronic acid biosynthesis via the myo-inositol oxidation pathway.
reference_section_type: RESULTS
- statement: >-
The myo-inositol oxidation pathway operates in the cytosol: myo-inositol is
converted to D-glucuronic acid (via MIOX), then to D-glucuronate-1-phosphate (via
glucuronokinase), then to UDP-glucuronic acid. This pathway provides metabolic
flexibility as an alternative to the UDP-glucose dehydrogenase route.
reference_section_type: RESULTS
- statement: >-
The closest characterized ortholog identified by phmmer is Arabidopsis GLAK2
(Q9LY82, probable glucuronokinase 2, EC 2.7.1.43), sharing the same GHMP kinase
domain architecture and glucuronokinase-like family membership.
reference_section_type: RESULTS
- id: GO_REF:0000002
title: Gene Ontology annotation through association of InterPro records with GO terms
findings: []
- id: GO_REF:0000033
title: Annotation inferences using phylogenetic trees
findings: []
- id: GO_REF:0000041
title: Gene Ontology annotation based on UniPathway vocabulary mapping
findings: []